Nosocomial (hospital-acquired) infections are the most common infection in the hospital setting with an estimated 2 million infections in the US each year resulting in about 90,000 deaths per year. Implant-related infections continue to be a major problem in surgery, and their occurrence is still significant despite measures in hospitals to limit patient infection in the operating room. For example, (i) mesh-related infections following hernia repair procedures have been reported to be as high as 8% after open incisional hernia repair with mesh (Falagas and Kasiakou, Mesh-related infections after hernia repair surgery, Clin. Microbiol. Infec. 11:3-8 (2005), (ii) rates of infection after breast implantation have been reported to range from 2.0-2.5% (Pittet, Infection in breast implants, Lancet Infect Dis. 5:94-106 (2005), (iii) the incidence of infections after hip and knee replacements in the US has been reported to be between 0.67% and 2.4%, and (iv) the incidence of infection in patients implanted with pacemakers is reported to have increased by 224% from 1.6% in 1993 to 3.5% in 2008.
In addition to efforts to reduce patient contamination both in the operating room and on the way to the operating room, medical device manufacturers have introduced various implants that contain antimicrobial agents to reduce or inhibit microbial colonization on a medical device, and to reduce or prevent device-related infections. For example, the Codman BACTISEAL® Catheter and Medtronic ARES® Catheter both contain clindamycin and rifampin to reduce infection when these devices are implanted to drain cerebrospinal fluid; Smith & Nephew's ORTHOGUARD® product contains gentamicin to prevent infection around orthopedic wires and pins; Gore's DUAL MESH® contains silver carbonate and chlorhexidine acetate to prevent infection after hernia and soft tissue repair; and Depuy's PROSTALAC® hip system contains tobramycin and vancomycin to prevent infection following total hip replacement.
Recently, a number of implantable devices made from, or containing, poly-4-hydroxybutyrate (P4HB), a resorbable thermoplastic polymer, have been introduced. For example, hernia repair products made from P4HB fibers have been disclosed by Martin et al. Characterization of poly-4-hydroxybutyrate mesh for hernia repair applications, J. Surg. Res. 184:766-773 (2013), and sutures made from P4HB monofilament have been disclosed by Odermatt et al. A new long-term absorbable monofilament suture made from poly-4-hydroxybutyrate, Journal of Polymer Science, 2012 Article 216137, 12 pages. Other P4HB medical devices have been disclosed by Williams et al. Poly-4-hydroxybutyrate (P4HB): a new generation of resorbable medical devices for tissue repair and regeneration. Biomed Tech (Berl), 2013, ISSN (Online) 1862-278X, ISSN (Print) 0013-5585, DOI: 10.1515/bmt-2013-0009. However, none of these P4HB devices contain antimicrobial agents to prevent colonization of the device and/or to reduce or prevent infection.
There is thus a need to develop implants of P4HB and copolymers thereof that contain and release one or more antimicrobial agents to prevent colonization of the implants and/or to reduce or prevent infection.
It is an object of the present invention to provide oriented implants of P4HB and copolymers thereof that contain one or more antimicrobial agents to prevent colonization of the implants and/or to reduce or prevent infection following implantation in a patient.
It is a further object of the present invention to provide processes to produce oriented implants of P4HB and copolymers thereof that contain antimicrobial agents suitable for the prevention of implant colonization and/or to reduce or prevent infection.
It is still another object of the invention to provide methods for implantation of oriented implants made from P4HB and copolymers thereof that contain antimicrobial agents.